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Infect Immun, February 1998, p. 676-681, Vol. 66, No. 2
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Proteolytic Activation of the Interleukin-1beta Precursor by Candida albicans

Annie Beauséjour, Daniel Grenier, Jean-Paul Goulet, and Noëlla Deslauriers*

Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire et Faculté des Sciences et de Génie, Université Laval, Québec, Québec, Canada

Received 16 June 1997/Returned for modification 28 July 1997/Accepted 21 November 1997

Chronic inflammation rather than invasion is characteristic of some forms of superficial candidiasis such as denture stomatitis. We hypothesized that Candida albicans may play a critical role in the pathogenesis of inflammatory lesions observed in chronic candidiasis by activating the proinflammatory cytokine interleukin-1beta (IL-1beta ) from epithelial stores of the precursor. The aim of this study was therefore to demonstrate the proteolytic cleavage and activation of the inactive precursor of IL-1beta (pro-IL-1beta ) by C. albicans. After incubation of either blastospores or hyphae with the inactive precursor, proteolytic cleavage was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western immunoblotting analysis, and the biological activity of the cleavage products was tested in a bioassay. We report here that late-stationary-growth-phase blastospores as well as hyphae of C. albicans, but not exponentially growing cells, can efficiently cleave pro-IL-1beta to yield fragments of molecular masses compatible with mature biologically active IL-1beta (17 to 19 kDa). Assays conducted in the presence of selected proteinase inhibitors suggest that the cleavage of pro-IL-1beta involves the participation of one or more aspartyl proteinases. Cleavage products showed a dose-dependent IL-1beta -like activity in a thymocyte proliferation bioassay, which was inhibited by anti-IL-1beta neutralizing antibodies. The present data thus suggest a role for C. albicans proteinases in the activation and maintenance of the inflammatory response at epithelial surfaces.

* Corresponding author. Mailing address: Groupe de Recherche en Écologie Buccale, Université Laval, Québec, Québec, Canada G1K 7P4. Phone: (418) 656-2067. Fax: (418) 656-2861. E-mail: Noella.Deslauriers{at}greb.ulaval.ca.




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